The objective of this study is to examine possible correlations between genetic differences in cleft palate susceptibility with genetic differences in cytochrome P-450-mediated monooxygenase activity in genetically homogeneous lines of mice. The median effective dosage (ED50) of cortisone acetate and 5,5-diphylhydantoin (PHT) required to induce cleft palate in A/J, DBA/1J, C57BL/6J and CBA/J mice will be determined. On gestation days 15 and 18 maternal liver and kidney and fetal liver and palatal shelf concentrations and/or activities of glucose-6-phosphate dehydrogenase, NADPH, NADH, cytochrome b5, cytochrome P-450, flavin adenine dinucleotide, flavin mononucleotide, and P-450-mediated hydroxalase will be determined in control, ED50 cortisone treated, and ED50 PHT treated groups of mice. The constitutive and induced levels of the above components will be examined statistically in order to identify possible correlations with the cleft palate incidence determined on gestation day 18. The cleft palate response and cytochrome P-450-mediated monooxygenase activity will also be determined in crosses and backcrosses between A/J x C57BL/6J and DBA/1J x CBA/J mice. The breeding studies will show how differences in constitutive and induced monooxygenase activities segregate and in the F2 generation of crosses between the pairs what the individual fetal variation in enzyme activities are. The information provided by these data will allow the efficient design of experiments the specific aims of which will be to identify protective or preventive measures which can be utilized by high genetic risk individuals prior to or following exposure to environmental teratogens.